Exploration of 5-Hydroxybowdichione Flavonoids As Inhibitors of Dengue Virus Ns5 RNA-Dependent RNA Polymerase Using Molecular Docking Approach

Year : 2023 | Volume :01 | Issue : 01 | Page : 1-16
By

Arshita Jindal

  1. Student Department of Biotechnology, Meerut Institute of Engineering and Technology Uttar Pradesh India

Abstract

Objectives: Human lives are now seriously threatened by dengue fever, which is brought on by the dengue virus (DENV). Aedes aegypti mosquitoes, which reproduce in still water, are the primary vectors of the arboviral virus known as dengue. It is well-recognized that phytochemicals have a high potential to eliminate bacterial, viral, and fungal infections in people. Thus, it demonstrates its inhibitory effects on the dengue virus. This study identifies some of the 5-hydroxybowdichione flavonoids’ natural dengue virus inhibitors. Methods: 5-hydroxybowdichione flavonoids were employed in a computational technique to evaluate the effective inhibitor against dengue virus NS5 RNA-dependent RNA polymerase. 15 flavonoids in total, including 5-hydroxybowdichione and its derivatives, were chosen. The findings analysis was carried out using a variety of methods and instruments. To identify the phytocompounds, PubChem was employed. Protein was retrieved from the Protein Data Bank and confirmed using a variety of tools, including the BIOVIA discovery studio software, PDBsum generates, and the Swiss model. The PyRx software was used to carry out the molecular docking. For the pharmacological research, ADMET studies on these flavonoids were conducted. Results: The ligands Cudraflavone-C, Paratocarpin-B, Paratocarpin-C, and Shancio-H have the lowest binding affinities and may have an inhibitory impact on DENV, according to the ADMET analysis and docking data. These ligands have the best ADMET characteristics and pose the least amount of hazardous risk. Conclusion: The best binding affinity for protein is -9.7, and it belongs to the ligand Shanciol-H. In vitro studies can be used to learn more about these substances

Keywords: ADMET, molecular docking, phytocompounds, RNA-dependent RNA polymerase, Dengue virus, 5-hydroxybowdichione.

[This article belongs to International Journal of Genetic Modifications and Recombinations(ijgmr)]

How to cite this article: Arshita Jindal. Exploration of 5-Hydroxybowdichione Flavonoids As Inhibitors of Dengue Virus Ns5 RNA-Dependent RNA Polymerase Using Molecular Docking Approach. International Journal of Genetic Modifications and Recombinations. 2023; 01(01):1-16.
How to cite this URL: Arshita Jindal. Exploration of 5-Hydroxybowdichione Flavonoids As Inhibitors of Dengue Virus Ns5 RNA-Dependent RNA Polymerase Using Molecular Docking Approach. International Journal of Genetic Modifications and Recombinations. 2023; 01(01):1-16. Available from: https://journals.stmjournals.com/ijgmr/article=2023/view=111632

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References

  1. Zou et al., “Functional analysis of two cavities in flavivirus NS5 polymerase.,” J. Biol. Chem., vol. 286, no. 16, pp. 14362–14372, Apr. 2011, doi: 10.1074/jbc.M110.214189.
  2. P. Lim et al., “A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities.,” J. Biol. Chem., vol. 288, no. 43, pp. 31105–31114, Oct. 2013, doi: 10.1074/jbc.M113.508606.
  3. Ochida et al., “Modeling present and future climate risk of dengue outbreak, a case study in New Caledonia,” Environ. Heal., vol. 21, no. 1, p. 20, 2022, doi: 10.1186/s12940-022-00829-z.
  4. X. Yu, J. W. Tan, K. Rullah, S. Imran, and C. L. Tham, “Insight parameter drug design for human β-tryptase inhibition integrated molecular docking, QSAR, molecular dynamics simulation, and pharmacophore modelling studies of α-keto-[1,2,4]-oxadiazoles,” bioRxiv, p. 2022.07.17.500327, Jan. 2022, doi: 10.1101/2022.07.17.500327.
  5. G. Guzmán and G. Kourí, “Dengue: an update.,” Lancet. Infect. Dis., vol. 2, no. 1, pp. 33–42, Jan. 2002, doi: 10.1016/s1473-3099(01)00171-2.
  6. C. Weaver and N. Vasilakis, “Molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease.,” Infect. Genet. Evol.  J. Mol. Epidemiol.  Evol. Genet. Infect. Dis., vol. 9, no. 4, pp. 523–540, Jul. 2009, doi: 10.1016/j.meegid.2009.02.003.
  7. L. Akey et al., “Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system.,” Science, vol. 343, no. 6173, pp. 881–885, Feb. 2014, doi: 10.1126/science.1247749.
  8. Tahir Ul Qamar et al., “In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach,” Pak. J. Pharm. Sci., vol. 30, pp. 2119–2137, Nov. 2017.
  9. L. Muñoz-Jordan, G. G. Sánchez-Burgos, M. Laurent-Rolle, and A. García-Sastre, “Inhibition of interferon signaling by dengue virus.,” Proc. Natl. Acad. Sci. U. S. A., vol. 100, no. 24, pp. 14333–14338, Nov. 2003, doi: 10.1073/pnas.2335168100.
  10. Troost and J. M. Smit, “Recent advances in antiviral drug development towards dengue virus.,” Curr. Opin. Virol., vol. 43, pp. 9–21, Aug. 2020, doi: 10.1016/j.coviro.2020.07.009.
  11. Bollati et al., “Structure and functionality in flavivirus NS-proteins: perspectives for drug design.,” Antiviral Res., vol. 87, no. 2, pp. 125–148, Aug. 2010, doi: 10.1016/j.antiviral.2009.11.009.
  12. P. Lim, C. G. Noble, and P.-Y. Shi, “The dengue virus NS5 protein as a target for drug discovery.,” Antiviral Res., vol. 119, pp. 57–67, Jul. 2015, doi: 10.1016/j.antiviral.2015.04.010.
  13. V Koonin, “Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus.,” J. Gen. Virol., vol. 74 ( Pt 4), pp. 733–740, Apr. 1993, doi: 10.1099/0022-1317-74-4-733.
  14. V Koonin, “The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses.,” J. Gen. Virol., vol. 72 ( Pt 9), pp. 2197–2206, Sep. 1991, doi: 10.1099/0022-1317-72-9-2197.
  15. F. Fatriansyah, R. K. Rizqillah, and M. Y. Yandi, “Molecular Docking and Molecular Dynamics Simulation of Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin against Polymerase of Dengue Virus,” J. Trop. Med., vol. 2022, p. 7254990, 2022, doi: 10.1155/2022/7254990.
  16. Picarazzi, I. Vicenti, F. Saladini, M. Zazzi, and M. Mori, “Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge.,” Molecules, vol. 25, no. 23, Dec. 2020, doi: 10.3390/molecules25235695.
  17. Lin, X. Li, and X. Lin, “A Review on Applications of Computational Methods in Drug Screening and Design.,” Molecules, vol. 25, no. 6, Mar. 2020, doi: 10.3390/molecules25061375.
  18. P. Allen, “Introduction to molecular dynamics simulation,” Comput. soft matter from Synth. Polym. to proteins, vol. 23, no. 1, pp. 1–28, 2004.
  19. R. Leach, B. K. Shoichet, and C. E. Peishoff, “Prediction of protein− ligand interactions. Docking and scoring: successes and gaps,” J. Med. Chem., vol. 49, no. 20, pp. 5851–5855, 2006.
  20. Trott and A. J. Olson, “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading,” J. Comput. Chem., vol. 31, no. 2, pp. 455–461, 2010.
  21. Rutz et al., “The LOTUS initiative for open knowledge management in natural products research,” Elife, vol. 11, p. e70780, 2022, doi: 10.7554/eLife.70780.
  22. Kim et al., “PubChem in 2021: new data content and improved web interfaces,” Nucleic Acids Res., vol. 49, no. D1, pp. D1388–D1395, Jan. 2021, doi: 10.1093/nar/gkaa971.
  23. M. O’Boyle, M. Banck, C. A. James, C. Morley, T. Vandermeersch, and G. R. Hutchison, “Open Babel: An open chemical toolbox,” J. Cheminform., vol. 3, no. 1, p. 33, 2011, doi: 10.1186/1758-2946-3-33.
  24. T. Leong et al., “Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution,” J. Virol., vol. 81, no. 9, pp. 4753–4765, May 2007, doi: 10.1128/JVI.02283-06.
  25. K. Burley et al., “RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences,” Nucleic Acids Res., vol. 49, no. D1, pp. D437–D451, Jan. 2021, doi: 10.1093/nar/gkaa1038.
  26. Waterhouse et al., “SWISS-MODEL: homology modelling of protein structures and complexes,” Nucleic Acids Res., vol. 46, no. W1, pp. W296–W303, Jul. 2018, doi: 10.1093/nar/gky427.
  27. Kumar and A. Arya, “Ramachandran Plot,” Dec. 2018.
  28. A. Hollingsworth and P. A. Karplus, “A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins.,” Biomol. Concepts, vol. 1, no. 3–4, pp. 271–283, Oct. 2010, doi: 10.1515/BMC.2010.022.
  29. -Y. Meng, H.-X. Zhang, M. Mezei, and M. Cui, “Molecular docking: a powerful approach for structure-based drug discovery.,” Curr. Comput. Aided. Drug Des., vol. 7, no. 2, pp. 146–157, Jun. 2011, doi: 10.2174/157340911795677602.
  30. Dallakyan and A. J. Olson, “Small-molecule library screening by docking with PyRx.,” Methods Mol. Biol., vol. 1263, pp. 243–250, 2015, doi: 10.1007/978-1-4939-2269-7_19.
  31. Guan et al., “ADMET-score – a comprehensive scoring function for evaluation of chemical drug-likeness.,” Medchemcomm, vol. 10, no. 1, pp. 148–157, Jan. 2019, doi: 10.1039/c8md00472b.
  32. Yang et al., “admetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties,” Bioinformatics, vol. 35, no. 6, pp. 1067–1069, Mar. 2019, doi: 10.1093/bioinformatics/bty707.
  33. A. Rodenhuis-Zybert, J. Wilschut, and J. M. Smit, “Dengue virus life cycle: viral and host factors modulating infectivity,” Cell. Mol. Life Sci., vol. 67, no. 16, pp. 2773–2786, 2010, doi: 10.1007/s00018-010-0357-z.
  34. D. Dwivedi, I. P. Tripathi, R. C. Tripathi, S. Bharadwaj, and S. K. Mishra, “Genomics, proteomics and evolution of dengue virus,” Brief. Funct. Genomics, vol. 16, no. 4, pp. 217–227, Jul. 2017, doi: 10.1093/bfgp/elw040.
  35. Hasan, S. F. Jamdar, M. Alalowi, and S. M. Al Ageel Al Beaiji, “Dengue virus: A global human threat: Review of literature.,” J. Int. Soc. Prev. Community Dent., vol. 6, no. 1, pp. 1–6, 2016, doi: 10.4103/2231-0762.175416.
  36. S. Salles et al., “History, epidemiology and diagnostics of dengue in the American and Brazilian contexts: a review,” Parasit. Vectors, vol. 11, no. 1, p. 264, 2018, doi: 10.1186/s13071-018-2830-8.
  37. Gupta, S. Srivastava, A. Jain, and U. C. Chaturvedi, “Dengue in India.,” Indian J. Med. Res., vol. 136, no. 3, pp. 373–390, Sep. 2012.
  38. Kapoor, L. Zhang, M. Ramachandra, J. Kusukawa, K. E. Ebner, and R. Padmanabhan, “Association between NS3 and NS5 Proteins of Dengue Virus Type 2 in the Putative RNA Replicase Is Linked to Differential Phosphorylation of NS5 *,” J. Biol. Chem., vol. 270, no. 32, pp. 19100–19106, 1995, doi: https://doi.org/10.1074/jbc.270.32.19100.
  39. Singh et al., “The dual role of phytochemicals on SARS-CoV-2 inhibition by targeting host and viral proteins,” J. Tradit. Complement. Med., vol. 12, no. 1, pp. 90–99, 2022, doi: https://doi.org/10.1016/j.jtcme.2021.09.001.
  40. Biswas et al., “Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach,” J. Trop. Med., vol. 2022, p. 7111786, 2022, doi: 10.1155/2022/7111786.
Regular Issue Subscription Original Research
Volume 01
Issue 01
Received March 2, 2023
Accepted March 10, 2023
Published June 28, 2023
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